AUTHOR=Li Haobo , Zhang Zhu , Weng Haoyi , Qiu Yuting , Zubiaur Pablo , Zhang Yu , Fan Guohui , Yang Peiran , Vuorinen Anna-Leena , Zuo Xianbo , Zhai Zhenguo , Wang Chen 

TITLE=Association between CES1 rs2244613 and the pharmacokinetics and safety of dabigatran: Meta-analysis and quantitative trait loci analysis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.959916

DOI=10.3389/fcvm.2022.959916

ISSN=2297-055X

ABSTRACT=Objective: The results of the research on the influence of the carboxylesterase 1 (CES1) gene rs2244613 genotype on the pharmacokinetics (PKs) and safety of dabigatran are controversial. Hence, a systematic analysis review was performed on the association between the PKs, safety of dabigatran and CES1 gene rs2244613. 
Methods: In addition to the three English databases (Web of Science, PubMed, and Embase), two Chinese databases (CNKI and Wanfang) have also been searched extensively. The mean differences (MD) and corresponding 95% confidence intervals (CIs) were applied to evaluate the differences between the dabigatran PKs and CES1 rs2244613 genotype. Odds ratio (OR) was used to determine the relationship between the CES1 rs2244613 genotype and the safety of dabigatran. 
Results: Ten studies (n = 2,777) were included. Compared to T allele patients, trough concentrations of dabigatran were significantly lower in G allele ones (MD: −8.00 ng/mL; 95% CI: −15.08 – −0.92; p = 0.03). The bleeding risk in G allele carriers was significantly lower than in T allele individuals (OR: 0.65; 95% CI: 0.44 – 0.96; p = 0.03). 
Conclusion: Our meta-analysis indicated a definite relation amongst the CES1 rs2244613 genotype and tolerability variations or pharmacokinetic fluctuations. T allele carriers showed higher dabigatran concentrations; therefore, they would benefit from a dose reduction.